Microchip pileup type chemical reaction system

ABSTRACT

A microchip pileup type chemical reaction system characterized in that a specified number of microchips, each having a reaction material liquid introducing section, a reaction product liquid discharge section and a reaction region, i.e. microchannels, interconnected therewith, are laid integrally in layers, the same kind of reaction material is introduced from the reaction material liquid introducing section into each microchip and the same kind of reaction product is collected from the reaction product liquid discharge section. The novel system for high efficiency chemical reaction makes the most use of the feature of microspace where general organic synthesis reaction is performed in the microchips while enabling mass synthesis.

TECHNICAL FIELD

The present invention relates to a microchip pileup type chemicalreaction system. Particularly, the invention relates to a microchippileup type chemical reaction system that enables highly efficientchemical reactions yielding few by-products to be constructed as a largescale synthesis reaction system by taking advantage of microchannelshaving microspaces.

BACKGROUND ART

It has been actively developed in recent years to form microchannels asfine grooves having an width of 500 μm or less on a several centimeterssquare substrate, and to use these microchannels as chemical reactionregions.

The present inventors have also noticed that the microchannel involvesvarious advantages for highly efficient chemical reactions such as shortmolecular diffusion distances, large specific interface areas and smallheat capacity, when the microspace of the liquid phase in themicrochannel is considered to be a chemical reaction field. Accordingly,the present inventors have applied the microchannel reaction system tovarious intermolecular chemical reactions such as complexing reactions,solvent extraction, immunological reactions, enzyme reactions andion-pair extraction reactions. Highly efficient chemical reactions areexpected to be proceeded in such reaction field since substance transfertime is shortened, solid-liquid or liquid-liquid interface reactionsbecome predominant, and heat energies are promptly transferred from orto the reaction system. However, few basic researches systematicallyinvestigating basic chemical reactions in the liquid phase in themicro-spaces have been reported today. While large scale synthesisrather than high efficiency should be particularly considered in usualorganic synthesis reactions, substantially no relations between minutequantity of reactions in the microchip and large scale synthesis havebeen investigated.

Accordingly, the object of the invention is to enable large scalesynthesis in the usual organic synthesis reactions carried out in themicrochip, while realizing highly efficient chemical reactions by takingadvantage of the features of the microspace.

DISCLOSURE OF INVENTION

The present invention for solving the problems above provides amicrochip pileup type chemical reaction system comprising a specifiednumber of integrally laminated microchips each having reaction materialliquid introducing sections, a reaction product liquid dischargesection, and microchannels as regions communicating therewith. The samekind of reaction material is introduced from the reaction materialliquid introducing sections into each microchip to perform the same kindof reaction in each reaction region microchannel, and the same kind ofreaction product is collected from the reaction product liquid dischargesection.

In the microchip pileup type chemical reaction system of the invention,the reaction material liquid introducing section of each microchipdirectly communicates with the reaction material liquid introducingsection of a microchip laminated thereon or thereunder, or with thereaction material liquid introducing sections laminated thereon andthereunder. The reaction product liquid discharge section of eachmicrochip directly communicates with the reaction product liquiddischarge section of a microchip laminated thereon or thereunder, orwith the reaction product liquid discharge sections laminated thereonand thereunder.

The microchip pileup type chemical reaction system of the inventioncomprises a specified number of integrally laminated microchip pileupmembers of the invention integrally assembled in parallel.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view showing an example of the system of theinvention.

FIG. 2 illustrates the modes of introduction of the material liquid anddischarge of the product liquid in the example shown in FIG. 1.

FIG. 3 is a perspective view showing an example different from theexample shown in FIGS. 1 and 2.

FIG. 4 is a perspective view showing a further different example.

BEST MODE FOR CARRYING OUT THE INVENTION

While the invention is featured as described above, embodiments of theinvention will be described hereinafter.

Since the object of chemical synthesis is large scale synthesis in mostof organic synthesis, it has been often pointed out that the absolutequantity of the product is important in utilizing the microchannel as areaction field. However, a combination of “microchip” and “organicsynthesis” that seems to be contradictory at first glance is actuallycompatible with each other considering that the reaction in themicrochip is highly efficient. On the contrary, the microchip can exerta greater effect than using conventional reaction vessels. The inventionenables the features to be realized.

No chemical technology investigations are not intrinsically needed inscale up, when the microchannel is used as the reaction field. A highlyefficient demand-dependent reaction system may be constructed bylaminating a specified number of microchips for complying withrespective demands, and by assembling a plurality of microchip systemsin parallel as disclosed in the invention.

As described previously, the microchips, each providing introducingsections of the reaction material solutions (A) and (B) and a dischargesection of the reaction product solution as well as a microchannels as areaction region with an width of several tens to several hundredsmicrons that communicate with the introducing sections and dischargesection, are integrally laminated as shown in FIG. 1 in the invention.The same kind of reaction material is introduced from the reactionmaterial liquid introducing sections, the same kind of reaction isperformed in the reaction region of each microchannel, and the same kindof reaction product is collected from the reaction product dischargesection in the microchip pileup type chemical reaction system.

As for the integrally laminating the microchips, Pyrex glass plates areused as the substrates of the microchip, and the plates are fused byheating with compression. However, various methods such as those knownin the art may be employed depending on the kind of the substrate.

In the microchip pileup type chemical reaction system of the inventionas shown in FIG. 1, the reaction material liquid introducing section ofeach microchip may directly communicate with the reaction materialliquid introducing section of a microchip laminated thereon orthereunder, or with the reaction material liquid introducing sectionslaminated thereon and thereunder. Alternatively, the reaction productliquid discharge section of each microchip may directly communicate withthe reaction product liquid discharge sections of the microchipslaminated thereon or thereunder, or with the reaction product liquiddischarge sections laminated thereon and thereunder.

In the system as described above, the microchannel in each floor isperforated with vertical holes having a sufficiently larger diameterthan the microchannel size as shown in FIG. 2. Consequently, the holesserve as pools for buffering the solution to send to each floor, and aspools for collecting the reaction product to discharge to the outside.For example, a Teflon tube is connected to each vertical hole, thereaction product solution is collected after allowing the materialsolution to react by flowing it with a pressurizing pump. As a result, aplurality of microchannels each having the same function as a singlemicrochip can be operated in parallel, and the yield of the reactionproduct per unit time may be increased by taking advantage of thecharacteristics of the reactor having several tens to several hundredsmicrons of microchannels.

In another aspect of the invention, the material solution introducingsection and reaction product solution discharge section may be connectedto each microchip or to an assembly of several microchips as shown inFIG. 3 in order to independently introduce and discharge the solutions,instead of forming the reaction system as a communicating structure.

Alternatively, the microchip pileup type chemical reaction system may beconstructed so that a specified number of integrally laminated microchippileup members are integrally assembled in parallel as shown in FIG. 4.

According to the pileup type chemical reaction system described in theembodiments above, productivity of the reaction is improved by takingadvantage of microspace reactions while enabling the production scale tobe flexibly controlled by permitting simple parallel synthesis to beproceeded. Consequently, large scale synthesis is possible whileenabling the risk of excess production by large scale synthesis to beavoided. It is also possible to simplify the system and rationalize thedevelopment process.

From the features as described above, the invention is applicable to notonly the mass production system, synthetic production of pharmaceuticalsbut also to a small scale production system by which many kinds ofrequired products are synthesized in required quantities.

The invention will be described in detail in an example in which apigment is synthesized in an oil/water two-phase flow.

In this reaction system, a resorcinol derivative dissolved in an oilphase is partitioned between the oil phase and aqueous phase, and themajor product formed is extracted again into the oil phase after a diazocoupling reaction between the resorcinol derivative and a diazoniumsalt. The reaction efficiency was evaluated by analyzing the organicphase after the reaction using a microchip comprising Y-shapedmicrochannels (a width of 250 μm and a depth of 100 μm) in a plane view.

It was confirmed that the reaction yield is evidently higher in thereaction in the microchips than in a macroscopic scale reaction. This isbecause the residence time of the major reaction product in the aqueousphase is so short in the reaction in the microchip having a largespecific interface area that the major product formed is efficientlyextracted into the organic phase. Since side reactions hardly advances,the reaction yield is considered to be relatively improved.

Investigations of chemical engineering conditions are not required atall in the synthesis system using the microchip, and the microchipsystem is applicable to mass production by simply piling up theplate-shaped chips, for example as shown in FIG. 4. The pileup spacerequired for realizing an annual production scale of 1 ton is calculatedto be about 0.4 m³ based on the calculated productivity per one sheet ofchip using the high yield synthesis system investigated as describedabove. It was shown that a small space is sufficient for massproduction.

Accordingly, it is easy to construct a demand-dependent synthesis systemby which many kinds of required products are synthesized in requiredquantities by high yield synthesis based on continuous feed of thematerials and adjustment of the pileup number of the microchip sheets,which have been difficult to realize in the conventional chemicalengineering.

It has been a leading fashion for investigating the micro-reactor tonotice mixing efficiencies between two liquids (molecular diffusion),and prompt removal of the heat of reaction. However, the invention hasconfirmed that high speed, high yield synthetic reactions with fewby-products are possible by taking advantage of the microspaces, and themethod of the invention is also compatible with mass production.

Industrial Applicability

As described in detail above, the invention provides a novel system forhighly efficient chemical reactions by taking advantage of themicrospaces, whereby large scale synthesis is possible by performinguniversally applicable organic synthesis reactions in the microchips.

1. A microchip pileup type chemical reaction system comprising aspecified number of integrally laminated microchips each having reactionmaterial liquid introducing sections, a reaction product liquiddischarge section, and microchannels as regions communicating therewith,wherein the same kind of reaction materials are introduced from thereaction material liquid introducing sections into each microchip toperform the same kind of reaction in each reaction region microchannel,and the same kind of reaction product is collected from the reactionproduct liquid discharge section.
 2. The microchip pileup type chemicalreaction system according to claim 1, wherein the reaction materialliquid introducing section of each microchip directly communicates withthe reaction material liquid introducing section of the microchiplaminated thereon or thereunder, or with the reaction material liquidintroducing sections laminated thereon and thereunder.
 3. The microchippileup type chemical reaction system according to claim 1, wherein thereaction product liquid discharge section of each microchip directlycommunicates with the reaction product liquid discharge section of amicrochip laminated thereon or thereunder, or with the reaction productliquid discharge sections laminated thereon and thereunder.
 4. Themicrochip pileup type chemical reaction system comprising a specifiednumber of integrally laminated microchip pileup members according toclaim 1 integrally assembled in parallel.
 5. The microchip pileup typechemical reaction system according to claim 2, wherein the reactionproduct liquid discharge section of each microchip directly communicateswith the reaction product liquid discharge section of a microchiplaminated thereon or thereunder, or with the reaction product liquiddischarge sections laminated thereon and thereunder.
 6. The microchippileup type chemical reaction system comprising a specified number ofintegrally laminated microchip pileup members according to claim 2integrally assembled in parallel.
 7. The microchip pileup type chemicalreaction system comprising a specified number of integrally laminatedmicrochip pileup members according to claim 3 integrally assembled inparallel.